REPLY
Isosorbide-5-Mononitrate in Angina Pectoris
Udho Thadani, MBBS
1 October 1994 | Volume 121 Issue 7 | Page 547
IN RESPONSE:
Poss and colleagues question the clinical significance of an increase in exercise duration and prevention of tolerance during twice-daily treatment with IS-5-MN because angina frequency was not decreased [1]. Angina frequency is a poor measure of drug efficacy [1]. Patients with stable angina pectoris restrict their activity to avoid unpleasant anginal attacks [2]. Patients often state that they have few episodes of angina during daily activities, and yet they experience angina during treadmill exercise at a relatively low work load [3], just as we observed. Seasonal changes in patients' outdoor activity can affect angina frequency.
Only patients who experienced angina of moderate severity during multistage treadmill exercise entered the study. Nonetheless, 13 patients in the placebo group and 13 patients in the IS-5-MN group reported no anginal attacks throughout the study. The weekly frequency of anginal attacks was low in most patients who were not required to have a minimum number of angina attacks per week to be eligible for the study. For these reasons, the clinical significance of a lack of change in angina frequency during IS-5-MN treatment compared with placebo is questionable.
We believe that the improved exercise tolerance of 90 seconds 2 hours after the morning dose, as well as during multistage treadmill exercise testing, is clinically significant. This magnitude of improvement in exercise duration is greater than that reported with isosorbide dinitrate [2] and widely used calcium channel blockers [3, 4] and is similar to that observed after administration of sublingual nitroglycerine [5]. This magnitude of increase in exercise duration during the third stage of treadmill exercise using a modified Bruce protocol may result in a substantial increase in walking distance on a flat surface or gentle hill during daily activities.
1. Thadani U, Maranda CR, Amsterdam E, Spaccavento L, Friedman RG, Chernoff R, et al. Lack of pharmacologic tolerance and rebound angina pectoris during twice-daily therapy with isosorbide-5-mononitrate. Ann Intern Med. 1994; 120:353-9.
2. Bassan MM. The day-long pattern of the antiangial effect of long-term three times daily administered isosorbide dinitrate. J Am Coll Cardiol. 1990; 16:936-40.
3. Bittar N, Corder CN, Eich R, McGrew FA, Paulk EA, Zellner S. Efficacy of nifedipine gastrointestinal therapeutic system in combination with ß blockers in the management of exertional angina. A multicenter study of 54 patients. Am J Med. 1987; 83(Suppl 6B):30-3.
4. Thadani U, Glasser S, Bittar N, Beach CL, for the Diltiazem CD Study Group. Dose response evaluation of once-daily therapy with diltiazem CD in angina pectoris (Abstract). Cardiovasc Drugs Ther. 1993; 7(Suppl 2):445.
5. Thadani U, Prasad R, Hamilton SF, Voyles WF, Doyle R, Karpow SA. Isosorbide-5-mononitrate in angina pectoris: plasma concentration and duration of effects after acute therapy. Clin Pharmacol Ther. 1987; 42:58-65.
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